Bariatric surgical procedures are effective options for long-term obesity treatment to obtain sustained weight loss and substantial improvement of comorbidities and quality of life. Reduced stomach volume and malabsorption are not the only means by which bariatric surgery improves insulin action and associated parameters; alterations in endocrine response are thought to play important roles in the beneficial effects . The aim of this study was to evaluate the effects of gastric sleeve surgery on glycaemic control, lipid profile, GH, IGF-1 and IGFBP-2 among the Saudi adult male population. GH and IGFBP-2 levels were increased after bariatric surgery, while IGF-1 level was not altered. Insulin sensitivity was increased, as reflected by a decrease in insulin level and HOMA-IR index.
The somatotropic axis has an important role in maintaining healthy conditions, and it is suppressed in obesity due to reduced GH and IGF-1 levels in the body. Hyperinsulinaemia and high circulating free fatty acids reduce IGFBP-1 production by the liver, which is responsible for reduced GH production from the pituitary and consequently low IGF-1 levels .
IGF-1 has an important role in GH activity and is related to its serum levels. Increased IGF-1 levels in obesity have a negative effect and cause GH suppression [20-21]. In the current study, GH was elevated after gastric sleeve surgery, while IGF-1 was not changed. Insulin can bind to the IGF-1 receptor, and IGF-1 can bind to the insulin receptor, and both stimulate growth and hypoglycaemic effects. Moreover, hybrid heterodimeric receptors can be formed consisting of an insulin and an IGF-1 receptor α-β dimer, which signal mainly IGF-1 . After bariatric surgery, GH was increased, but IGF-1 was not. It is possible that IGF-1 signalling is enhanced since HOMA-IR was improved. High, low and normal levels of IGF-1 have been reported in obese populations [19-20]. Our results are in agreement with previous studies reporting no change in IGF levels postoperatively [23, 24]. However, an earlier decrease (3 weeks to 1 month) and an increase 1 year after bariatric surgery have also been reported [25, 26]. In obese children, reduced GH is not associated with decreased levels of IGF-1 or reduced somatic growth . In our study, cholesterol, HDL and LDL were increased after bariatric surgery, but they were still within the desired physiological levels. An increase in the lipid profile can be explained by the lipolytic effects of GH and the release of free fatty acids from visceral adipose tissue and, to a lesser extent, from subcutaneous fat by increasing hormone-sensitive lipase (HSL). Furthermore, GH maintains triglyceride storage in the liver by either inhibiting triglyceride lipolysis via HSL or oxidation by PPARγ . GH also stimulates triglyceride uptake into skeletal muscle to be used for energy or stored as intramyocellular lipids . Furthermore, as a result of bariatric surgery, calorie intake is reduced, which might lead to increased GH levels since its secretion is stimulated by hypoglycaemia. Increased GH after bariatric surgery has beneficial effects on maintaining proper glucose levels and preventing liver steatosis. In the liver, GH stimulates autophagy and preserves plasma glucose levels in chronically starved mice . Moreover, GH signalling in the liver is essential to regulate intrahepatic lipid metabolism, while IGF-1 helps in reducing the catabolic effects of GH . In the current study, although the elevated levels of TC, LDL and HDL may be in part due to increased GH level, there are several potential reasons for this, and not just attributable to increased GH levels.
IGFBP-2 is the main IGF-binding protein associated with regulating body weight and homeostasis and protects against obesity and insulin resistance [10, 31-33]. Obesity-related hyperinsulinaemia increases IGF-1 and inhibits IGFBP-2 secretion . In our study, IGFBP-2 was increased, while insulin level, HOMA-IR index and BMI were reduced 6-12 months after gastric sleeve surgery. IGFBP-2 concentration has been associated with improvements in insulin sensitivity, BMI and lipid profile in obesity-related studies. A recent 20-year longitudinal study of ageing has shown that IGFBP-2 level increases with age, positively correlates with insulin sensitivity, and negatively correlates with BMI at baseline and follow-up . In obese children, circulating levels of IGFBP‐2 correlate negatively with body mass and positively with insulin sensitivity . A recent animal study has shown that metformin upregulates IGFBP-2 production through activation of the AMPK-Sirt1-PPARα signalling pathway . Metformin-treated diabetic patients have higher IGFBP-2 levels and lower serum IGF1 levels than untreated patients . This highlights IGFBP-2 as a novel target for metformin action and AMPK-Sirt1-PPARα as a novel pathway to control metabolic syndrome. IGFBP-2 was shown to be increased after biliopancreatic diversion in obese patients and was associated with improved glucose and lipid levels that were sustained even after one year of follow-up . IGFBP-2 has also been shown to be regulated by leptin and may mediate some of leptin’s antidiabetic effects . Early increased levels of IGFBP-2 were noticed after gastric bypass but normalized shortly after . It was recently reported that higher basal levels of IGFBP-2 were associated with lower risk of metabolic syndrome and type 2 diabetes and its levels increased after bariatric surgery . In the current study, the role of IGFBP-2 is suggested to potentially mediate some of the beneficial effects of the sleeve gastrectomy in a healthy male population.
Our study subjects were a small number of homogenous males without medical complications. Future studies should be conducted in a larger sample including women and control lean subjects undergoing non-bariatric laparoscopic surgery for comparison.